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1.
Geroscience ; 46(1): 841-852, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37217631

RESUMO

In humans, social participation and integration wane with advanced age, a pattern hypothesized to stem from cognitive or physical decrements. Similar age-related decreases in social participation have been observed in several nonhuman primate species. Here, we investigated cross-sectional age-related associations between social interactions, activity patterns, and cognitive function in 25 group-living female vervets (a.k.a. African green monkeys, Chlorocebus sabaeus) aged 8-29 years. Time spent in affiliative behavior decreased with age, and time spent alone correspondingly increased. Furthermore, time spent grooming others decreased with age, but the amount of grooming received did not. The number of social partners to whom individuals directed grooming also decreased with age. Grooming patterns mirrored physical activity levels, which also decreased with age. The relationship between age and grooming time was mediated, in part, by cognitive performance. Specifically, executive function significantly mediated age's effect on time spent in grooming interactions. In contrast, we did not find evidence that physical performance mediated age-related variation in social participation. Taken together, our results suggest that aging female vervets were not socially excluded but decreasingly engaged in social behavior, and that cognitive deficits may underlie this relationship.


Assuntos
Função Executiva , Comportamento Social , Humanos , Animais , Chlorocebus aethiops , Feminino , Estudos Transversais , Envelhecimento , Integração Social
2.
Am J Primatol ; 86(2): e23582, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38050788

RESUMO

Nonhuman primates (NHPs) are valuable models for studying healthspan, including frailty development. Frailty metrics in people centers on functional measures, including usual gait speed which can be predictive of all-cause mortality. This concept that physical competencies are able to prognosticate an individual's health trajectory over chronologic aging is well-accepted and has led to refinements in how physical function is evaluated, and include measures of strength and power along with walking speed. NHP studies of aging require evaluation of physical function, which can be difficult in field and research settings. We compared stair climb velocity to usual walking speed in 28 peri-geriatric to geriatric NHPs, as incorporating a climbing obstacle integrates multiple components of physical function: isolated leg and back strength, proprioception, balance, and range of motion. We find that stair climbing speed was reliable between observers, and whether timing was in-person take from video capture. The stair climb rates were 50% more associated with chronological age than walking speed (R = -0.68 vs. -0.45) and only stair climbing speeds were retained as predictive of age when walking speed and bodyweight were included in multivariate models (overall R2 = 0.44; p < 0.0001). When comparing young (10-16 years) versus geriatric (16-29 years) stair climbing speed was significantly different (p < 0.001), while walking speeds only tended to be slower (p = 0.12) suggesting that the additional challenge of a stair climb better unmasks subclinical frailty development that usual walking speed.


Assuntos
Fragilidade , Animais , Envelhecimento , Primatas
3.
J Dairy Sci ; 106(12): 9663-9676, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37641349

RESUMO

l-Glutamine supplementation improves gastrointestinal and immune function in dairy calves during controlled immune and stress challenges. However, it is unknown whether supplementing milk replacer (MR) with l-glutamine improves preweaning dairy calf health and welfare under production conditions. Therefore, the study objective was to evaluate the effects of supplementing MR with l-glutamine on gastrointestinal permeability, immune function, growth performance, postabsorptive metabolic biomarkers, and physiological stress response in preweaning dairy calves. In 3 repetitions, Holstein heifer calves (n = 30; 1.5 ± 0.5 d old; 37.1 ± 0.86 kg body weight) were blocked by serum total protein, body weight, and age, and provided MR (3.8 L/calf per d; 24% CP, 17% fat, 12.5% solids) supplemented with l-glutamine (GLN; 10g/kg MR powder; n = 5 calves/repetition) or nonsupplemented (NSMR; n = 5 calves/repetition). Calves were individually housed with ad libitum starter grain and water access until weaning (56.4 ± 0.5 d old). At 1 and 6 wk of age, urinary catheters were placed, and calves were orally dosed with 1 L of chromium (Cr)-EDTA. Urine samples were collected over a 24-h period for Cr output analysis as an in vivo biomarker of gastrointestinal permeability. Blood was collected on study d 1, 5, 7, 14, 21, 42, and 56 to measure white blood cell counts, cortisol, insulin, glucose, nonesterified fatty acids, serum amyloid A, haptoglobin, and neutrophil: lymphocytes. Two study intervals were used in the statistical analyses, representing greater (P1; wk 1-3) and reduced (P2; wk 4-8) enteric disease susceptibility. Data were analyzed using PROC GLIMMIX in SAS 9.4 (SAS Institute Inc.) with calf as the experimental unit. Overall, total urinary Cr output was reduced in GLN versus NSMR calves. Total Cr output was reduced at 1 wk of age in GLN versus NSMR calves, but no differences were detected at 6 wk of age. Neutrophil:lymphocyte was decreased both overall and during P2 in GLN versus NSMR calves, and neutrophil counts tended to be reduced in GLN versus NSMR calves during P2. No MR treatment differences were detected for average daily feed intake, average daily gain, body measurements, postabsorptive metabolic biomarkers, disease scores, and therapeutic treatments between GLN and NSMR calves. In summary, l-glutamine supplementation reduced gastrointestinal permeability and biomarkers of physiological stress in preweaning Holstein heifer calves.


Assuntos
Dieta , Glutamina , Animais , Bovinos , Feminino , Dieta/veterinária , Glutamina/farmacologia , Desmame , Suplementos Nutricionais , Peso Corporal/fisiologia , Leite/química , Estresse Fisiológico , Ração Animal/análise , Biomarcadores , Ácido Edético/análise
4.
J Med Chem ; 66(13): 9120-9129, 2023 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-37315328

RESUMO

G-protein-coupled receptor 119 (GPR119) has emerged as a promising target for treating type 2 diabetes mellitus. Activating GPR119 improves glucose homeostasis, while suppressing appetite and weight gain. Measuring GPR119 levels in vivo could significantly advance GPR119-based drug development strategies including target engagement, occupancy, and distribution studies. To date, no positron emission tomography (PET) ligands are available to image GPR119. In this paper, we report the synthesis, radiolabeling, and preliminary biological evaluations of a novel PET radiotracer [18F]KSS3 to image GPR119. PET imaging will provide information on GPR119 changes with diabetic glycemic loads and the efficacy of GPR119 agonists as antidiabetic drugs. Our results demonstrate [18F]KSS3's high radiochemical purity, specific activity, cellular uptake, and in vivo and ex vivo uptake in pancreas, liver, and gut regions, with high GPR119 expression. Cell pretreatment with nonradioactive KSS3, rodent PET imaging, biodistribution, and autoradiography studies showed significant blocking in the pancreas showing [18F]KSS3's high specificity.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Ligantes , Diabetes Mellitus Tipo 2/tratamento farmacológico , Radioquímica , Distribuição Tecidual , Tomografia por Emissão de Pósitrons/métodos , Radioisótopos de Flúor , Receptores Acoplados a Proteínas G/metabolismo
5.
NPJ Vaccines ; 8(1): 45, 2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-36949051

RESUMO

Respiratory syncytial virus (RSV) is a leading cause of severe respiratory disease for which no licensed vaccine is available. We have previously shown that a prefusion (preF) conformation-stabilized RSV F protein antigen and an adenoviral vector encoding RSV preF protein (Ad26.RSV.preF) are immunogenic and protective in animals when administered as single components. Here, we evaluated a combination of the 2 components, administered as a single injection. Strong induction of both humoral and cellular responses was shown in RSV-naïve and pre-exposed mice and pre-exposed African green monkeys (AGMs). Both components of the combination vaccine contributed to humoral immune responses, while the Ad26.RSV.preF component was the main contributor to cellular immune responses in both mice and AGMs. Immunization with the combination elicited superior protection against RSV A2 challenge in cotton rats. These results demonstrate the advantage of a combination vaccine and support further clinical development.

6.
Obesity (Silver Spring) ; 31 Suppl 1: 75-84, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36229981

RESUMO

OBJECTIVE: Time-restricted feeding (TRF), whereby caloric intake is limited to a <12-hour window, is a potential regimen to ameliorate metabolic syndrome and cardiovascular disease (CVD) risk co-occurring with aging and with obesity. Early TRF (eTRF; early morning feeding followed by overnight fasting) times calorie consumption with hepatic circadian gene expression rhythms. Brief TRF trials demonstrate that high-density lipoprotein (HDL) cholesterol increases similar to diet/exercise interventions, which may impart beneficial CVD effects. Using a nonhuman primate (NHP) model, the efficacy of eTRF to raise HDL and increase plasma cholesterol efflux capacity (CEC) (primarily mediated by cholesterol efflux to HDL particles, a process that is inversely associated with CVD risk) was examined. METHODS: Adult (8-16 years old, n = 25) and geriatric (≥17 years old) NHPs were randomized to ad libitum feeding or eTRF for 12 months, and relevant body composition, glycemic control, and plasma HDL cholesterol levels and CEC were measured. RESULTS: Impaired CEC was found in geriatric NHPs. eTRF induced larger-sized HDL particles, increased HDL apolipoprotein A-1 content, lowered triglyceride concentrations, and increased plasma CEC (primarily to HDL particles) in both adult and geriatric NHPs without changes in glycemic control or body composition. CONCLUSIONS: A beneficial effect of eTRF on increasing HDL CEC in NHPs was demonstrated.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Doenças Cardiovasculares , Jejum Intermitente , Primatas , Animais , Composição Corporal , Doenças Cardiovasculares/dietoterapia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/veterinária , HDL-Colesterol , Lipoproteínas HDL/metabolismo , Primatas/metabolismo
7.
Front Vet Sci ; 9: 922961, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36504866

RESUMO

Yersinia enterocolitica is a Gram-negative bacterium that typical results in enterocolitis in humans and poses significant worldwide risks to public health. An outbreak of yersiniosis in the Vervet/African green monkey colony at the WFSM during the winter of 2015-2016 accounted for widespread systemic infection with high morbidity and mortality. Most of the cases had extensive necrosis with suppuration and large colonies of bacilli in the large bowel and associated lymph nodes; however, the small intestine, stomach, and other organs were also regularly affected. Positive cultures of Yersinia enterocolitica were recovered from affected tissues in 20 of the 23 cases. Carrier animals in the colony were suspected as the source of the infection because many clinically normal animals were culture-positive during and after the outbreak. In this study, we describe the gross and histology findings and immune cell profiles in different organs of affected animals. We found increased numbers of myeloid-derived phagocytes and CD11C-positive antigen-presenting cells and fewer adaptive T and B lymphocytes, suggesting an immunocompromised state in these animals. The pathogen-mediated microenvironment may have contributed to the immunosuppression and rapid spread of the infection in the vervets. Further studies in vervets could provide a better understanding of Yersinia-mediated pathogenesis and immunosuppression, which could be fundamental to understanding chronic and systemic inflammatory diseases in humans.

8.
Exp Biol Med (Maywood) ; 247(23): 2103-2118, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36000165

RESUMO

Alginate, a naturally occurring polysaccharide, has been widely used in cell encapsulation, 3D culture, cell therapy, tissue engineering, and regenerative medicine. Alginate's frequent use comes from its biocompatibility and ability to easily form hydrogel in a variety of forms (e.g. microcapsules, microfibers, and porous scaffolds), which can provide immunoprotection for cell therapy and mimic the extracellular matrix for tissue engineering. During the past 15 years, alginate hydrogel microfibers have attracted more and more attention due to its continuous thin tubular structures (diameter or shell thickness ⩽ 200 µm), high-density cell growth, high handleability and retrievability, and scalability. This review article provides a concise overview of alginate and its resultant hydrogel microfibers for the purpose of promoting multidisciplinary, collaborative, and convergent research in the field. It starts with a historical review of alginate as biomaterials and provides basics about alginate structure, properties, and mechanisms of hydrogel formation, followed by current challenges in effective cell delivery and functional tissue engineering. In particular, this work discusses how alginate microfiber technology could provide solutions to unmet needs with a focus on the current state of the art of alginate microfiber technology and its applications in 3D cell culture, cell delivery, and tissue engineering. At last, we discuss future directions in the perspective of alginate-based advanced technology development in biology and medicine.


Assuntos
Alginatos , Alicerces Teciduais , Alicerces Teciduais/química , Alginatos/química , Materiais Biocompatíveis/química , Engenharia Tecidual , Hidrogéis/química
9.
J Anim Sci ; 100(8)2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35679611

RESUMO

Oral administration of indigestible markers and subsequent urine collection is a useful method to determine in vivo gastrointestinal tract (GIT) permeability in cattle for research purposes. However, urine sampling techniques often rely on total waste collection, which reduces the ability to perform more frequent sampling and obtain accurate volumes and sterile samples. An alternative is urethral catheterization, though the feasibility of this technique has not been thoroughly tested in preweaned Holstein heifer calves. The study objective was to develop a urethral catheter placement procedure in preweaned Holstein heifer calves for continuous and accurate urine collection to evaluate GIT permeability using an indigestible marker. Fifteen Holstein heifer calves had catheters placed at approximately 1 wk (8.0 ± 1.5 d) and 6 wk (40.0 ± 1.5 d) of age. During the procedure, calves were individually housed and restrained. The vulva was sterilized and then a sterile, lubricated speculum was inserted into the vagina. A sterile 0.09 cm diameter guidewire was guided into a lubricated, sterile 10 French Foley catheter. The catheter was inserted at approximately 5 through 7 cm into the urethral opening, guided into the bladder, and the catheter balloon was filled with 10 mL of water. The guidewire was removed, and urine flow confirmed correct placement before a 4-L urinary drainage bag was attached to the catheter. After catheterization (24 h), 1 L of chromium (Cr)-ethylenediaminetetraacetic acid was orally dosed to the calves. Calf health observations were made six times over a 48-h period, and any occurrence of vaginal discharge, tissue discharge in catheter, bleeding, inflammation, or abnormal urine was considered a localized reaction. The proportion of localized reactions for each age group was determined using Microsoft Excel, and the total Cr output was analyzed using PROC GLIMMIX. Localized reactions occurred for 20.0% of the 1-wk-old calves and 13.3% of the 6-wk-old calves. In the first 4 h, urine was collected every 15 min, and there were no overall Cr output differences (P = 0.38; 10.28 ± 3.21 mg Cr) when comparing 1- and 6-wk-old calves. However, 1-wk-old calves tended (P = 0.08) to have greater overall Cr output at 480 min (19.2%) and 1,440 min (41.9%) when compared with 6-wk-old calves. In summary, urinary catheterization is a viable urinary collection method for the determination of in vivo GIT permeability in preweaned Holstein heifer calves.


Neonatal calves are highly susceptible to enteric disease during their first few weeks of life, and enteric disease is the leading cause of preweaning morbidity and mortality. A consequence of enteric disease is greater gastrointestinal tract (GIT) permeability in neonatal calves, which is also influenced by reduced intestinal maturity and environmental factors. Therefore, an accurate and precise method of evaluating GIT permeability in neonatal calves is necessary to develop appropriate treatment and mitigation strategies. The oral administration of indigestible markers and measurement of their presence in urine is an accepted method to determine the total GIT permeability in mature heifers. However, current urine collection methods in preweaned heifer calves may not be reliable. Therefore, the study objective was to develop a urinary catheterization method to collect urine accurately and precisely for the in vivo determination of GIT permeability in 1- and 6-wk-old Holstein heifer calves. It was determined that the urinary catheterization procedure and collection system developed in this study were viable and could be applied when evaluating GIT permeability in preweaned Holstein heifer calves using orally dosed indigestible markers.


Assuntos
Trato Gastrointestinal , Cateteres Urinários , Ração Animal , Animais , Bovinos , Dieta/veterinária , Feminino , Intestinos , Permeabilidade , Desmame
10.
iScience ; 25(3): 103948, 2022 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-35265817

RESUMO

Maternal parity can impact offspring growth, but the mechanisms driving this effect are unclear. Here, we test the hypothesis that vertically transmitted microbiota may be one potential mechanism. We analyzed 118 fecal and milk samples from mother-offspring vervet monkey dyads across the first 6 months of life. Despite poorer milk production, offspring born to low parity females grew larger than their counterparts. These offspring exhibited reduced alpha diversity in the first days of life, stronger seeding of maternal milk microbiota, Bacteroides fragilis dominance, and a greater abundance of glycan utilization pathways. Moreover, the attainment of greater body mass by 6 months of age was mediated by reduced early life alpha diversity and B. fragilis dominance. This work demonstrates that the establishment of a specialized, milk-oriented gut microbiota promotes infant growth and suggests an evolutionarily conserved developmental role of B. fragilis in primates.

11.
Bioengineering (Basel) ; 9(1)2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35049747

RESUMO

Understanding the different regulatory functions of epithelial and mesenchymal cell types in salivary gland development and cellular organization is essential for proper organoid formation and salivary gland tissue regeneration. Here, we demonstrate a biocompatible platform using pre-formed alginate hydrogel microtubes to facilitate direct epithelial-mesenchymal cell interaction for 3D salivary gland cell organization, which allows for monitoring cellular organization while providing a protective barrier from cell-cluster loss during medium changes. Using mouse salivary gland ductal epithelial SIMS cells as the epithelial model cell type and NIH 3T3 fibroblasts or primary E16 salivary mesenchyme cells as the stromal model cell types, self-organization from epithelial-mesenchymal interaction was examined. We observed that epithelial and mesenchymal cells undergo aggregation on day 1, cavitation by day 4, and generation of an EpCAM-expressing epithelial cell layer as early as day 7 of the co-culture in hydrogel microtubes, demonstrating the utility of hydrogel microtubes to facilitate heterotypic cell-cell interactions to form cavitated organoids. Thus, pre-formed alginate microtubes are a promising co-culture method for further understanding epithelial and mesenchymal interaction during tissue morphogenesis and for future practical applications in regenerative medicine.

12.
Geroscience ; 44(2): 699-717, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34591235

RESUMO

DNA methylation-based biomarkers of aging have been developed for many mammals but not yet for the vervet monkey (Chlorocebus sabaeus), which is a valuable non-human primate model for biomedical studies. We generated novel DNA methylation data from vervet cerebral cortex, blood, and liver using highly conserved mammalian CpGs represented on a custom array (HorvathMammalMethylChip40). We present six DNA methylation-based estimators of age: vervet multi-tissue epigenetic clock and tissue-specific clocks for brain cortex, blood, and liver. In addition, we developed two dual species clocks (human-vervet clocks) for measuring chronological age and relative age, respectively. Relative age was defined as ratio of chronological age to maximum lifespan to address the species differences in maximum lifespan. The high accuracy of the human-vervet clocks demonstrates that epigenetic aging processes are evolutionary conserved in primates. When applying these vervet clocks to tissue samples from another primate species, rhesus macaque, we observed high age correlations but strong offsets. We characterized CpGs that correlate significantly with age in the vervet. CpG probes that gain methylation with age across tissues were located near the targets of Polycomb proteins SUZ12 and EED and genes possessing the trimethylated H3K27 mark in their promoters. The epigenetic clocks are expected to be useful for anti-aging studies in vervets.


Assuntos
Epigênese Genética , Epigenômica , Animais , Chlorocebus aethiops , Metilação de DNA , Longevidade , Macaca mulatta/genética , Mamíferos
13.
Animals (Basel) ; 11(10)2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34680000

RESUMO

Data governance is a growing concern in the dairy farm industry because of the lack of legal regulation. In this commentary paper, we discuss the status quo of the available legislation and codes, as well as some possible solutions. To our knowledge, there are currently four codes of practice that address agriculture data worldwide, and their objectives are similar: (1) raise awareness of diverse data challenges such as data sharing and data privacy, (2) provide data security, and (3) illustrate the importance of the transparency of terms and conditions of data sharing contracts. However, all these codes are voluntary, which limits their adoption. We propose a Farmers Bill of Rights for the dairy data ecosystem to address some key components around data ownership and transparency in data sharing. Our hope is to start the discussion to create a balanced environment to promote equity within the data economy, encourage proper data stewardship, and to foster trust and harmony between the industry companies and the farmers when it comes to sharing data.

14.
Animals (Basel) ; 11(7)2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34359153

RESUMO

Dairy farm decision support systems (DSS) are tools which help dairy farmers to solve complex problems by improving the decision-making processes. In this paper, we are interested in newer generation, integrated DSS (IDSS), which additionally and concurrently: (1) receive continuous data feed from on-farm and off-farm data collection systems and (2) integrate more than one data stream to produce insightful outcomes. The scientific community and the allied dairy community have not been successful in developing, disseminating, and promoting a sustained adoption of IDSS. Thus, this paper identifies barriers to adoption as well as factors that would promote the sustained adoption of IDSS. The main barriers to adoption discussed include perceived lack of a good value proposition, complexities of practical application, and ease of use; and IDSS challenges related to data collection, data standards, data integration, and data shareability. Success in the sustainable adoption of IDSS depends on solving these problems and also addressing intrinsic issues related to the development, maintenance, and functioning of IDSS. There is a need for coordinated action by all the main stakeholders in the dairy sector to realize the potential benefits of IDSS, including all important players in the dairy industry production and distribution chain.

16.
Int J Surg Case Rep ; 85: 106141, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34330069

RESUMO

INTRODUCTION: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a form of temporary mechanical circulatory support commonly used during cardiothoracic interventions. Malperfusion during complex vascular procedures remains a significant risk that may potentially lead to multiple complications. Here, we report two cases highlighting the efficacy of VA-ECMO in both planned and emergent vascular interventions. PRESENTATION OF CASE: In our first case, VA-ECMO was used to support an 82-year-old male during a high-risk thoracoabdominal aortic aneurysm repair. Our second case details an emergent pulmonary embolectomy in which VA-ECMO was used as a bridge to cardiopulmonary bypass. In both cases, the procedures were well-tolerated, and the patients were discharged 17 days postoperatively. DISCUSSION: VA-ECMO has been increasingly used as a form of post-operative circulatory support following cardiothoracic and vascular interventions. However, only few instances of perioperative VA-ECMO use have been reported in the field of vascular surgery. CONCLUSION: The presented cases highlight that the perioperative use of VA-ECMO may be a viable modality for required perfusion during complex planned or emergent vascular procedures.

17.
Biomed Instrum Technol ; 55(2): 69-84, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34043008

RESUMO

To ensure patient safety, medical device manufacturers are required by the Food and Drug Administration and other regulatory bodies to perform biocompatibility evaluations on their devices per standards, such as the AAMI-approved ISO 10993-1:2018 (ANSI/AAMI/ISO 10993-1:2018).However, some of these biological tests (e.g., systemic toxicity studies) have long lead times and are costly, which may hinder the release of new medical devices. In recent years, an alternative method using a risk-based approach for evaluating the toxicity (or biocompatibility) profile of chemicals and materials used in medical devices has become more mainstream. This approach is used as a complement to or substitute for traditional testing methods (e.g., systemic toxicity endpoints). Regardless of the approach, the one test still used routinely in initial screening is the cytotoxicity test, which is based on an in vitro cell culture system to evaluate potential biocompatibility effects of the final finished form of a medical device. However, it is known that this sensitive test is not always compatible with specific materials and can lead to failing cytotoxicity scores and an incorrect assumption of potential biological or toxicological adverse effects. This article discusses the common culprits of in vitro cytotoxicity failures, as well as describes the regulatory-approved methodology for cytotoxicity testing and the approach of using toxicological risk assessment to address clinical relevance of cytotoxicity failures for medical devices. Further, discrepancies among test results from in vitro tests, use of published half-maximal inhibitory concentration data, and the derivation of their relationship to tolerable exposure limits, reference doses, or no observed adverse effect levels are highlighted to demonstrate that although cytotoxicity tests in general are regarded as a useful sensitive screening assays, specific medical device materials are not compatible with these cellular/in vitro systems. For these cases, the results should be analyzed using more clinically relevant approaches (e.g., through chemical analysis or written risk assessment).


Assuntos
United States Food and Drug Administration , Humanos , Estados Unidos
18.
Biofabrication ; 13(3)2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-33930885

RESUMO

Alginate hydrogels in microtubular structures have great potential to advance three-dimensional (3D) culture, organoid formation, tissue engineering, and cell therapy. To address the need of fabricating consistent, stable hydrogel microtubes for efficient large organoid generation in a simple and quick manner, we have designed needle-in-needle devices to fabricate alginate hydrogel microtubes without any dead volume of the cell-alginate mixture and demonstrated the feasibility of injecting and culturing embryoid bodies in these pre-made hydrogel microtubes. We further used a reverse engineering approach to find out the optimal flow rates and alginate concentration for fabricating pre-made hydrogel microtubes with desired diameter using particular sets of needle-in-needle devices. We established the relationship of the alginate flow rate with diameter and wall thickness of the microtube using mathematic modeling. It offers a way to determine the flow rate for making microtubes with the desired dimension. Additionally, we evaluated the effect of CaCl2concentration on the diameter as well as stem cell viability. At last, we demonstrated the capacity of fabricating hydrogel microtubes of varying diameters using three sets of needle-in-needle devices and evaluated stem cell growth in these hydrogel microtubes. It provides a new avenue to accessible, repeatable, scalable, and easy to use pre-made 'off-the-shelf' hydrogel microtubes for 3D cell culture including, but not limiting to stem cells.


Assuntos
Hidrogéis , Alginatos , Técnicas de Cultura de Células , Sobrevivência Celular , Corpos Embrioides , Células-Tronco , Engenharia Tecidual
19.
J Med Primatol ; 50(3): 176-181, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33876458

RESUMO

BACKGROUND: Whole-exome sequencing (WES) can expedite research on genetic variation in non-human primate (NHP) models of human diseases. However, NHP-specific reagents for exome capture are not available. This study reports the use of human-specific capture reagents in WES for olive baboons, marmosets, and vervet monkeys. METHODS: Exome capture was carried out using the SureSelect Human All Exon V6 panel from Agilent Technologies, followed by high-throughput sequencing. Capture of protein-coding genes and detection of single nucleotide variants were evaluated. RESULTS: Exome capture and sequencing results showed that more than 97% of old world and 93% of new world monkey protein coding genes were detected. Single nucleotide variants were detected across the genomes and missense variants were found in genes associated with human diseases. CONCLUSIONS: A cost-effective approach based on commercial, human-specific reagents can be used to perform WES for the discovery of genetic variants in these NHP species.


Assuntos
Exoma , Sequenciamento de Nucleotídeos em Larga Escala , Animais , Chlorocebus aethiops , Exoma/genética , Humanos , Indicadores e Reagentes , Primatas , Sequenciamento do Exoma
20.
Geroscience ; 43(3): 1303-1315, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33611720

RESUMO

Dual declines in gait speed and cognitive performance are associated with increased risk of developing dementia. Characterizing the patterns of such impairments therefore is paramount to distinguishing healthy from pathological aging. Nonhuman primates such as vervet/African green monkeys (Chlorocebus aethiops sabaeus) are important models of human neurocognitive aging, yet the trajectory of dual decline has not been characterized. We therefore (1) assessed whether cognitive and physical performance (i.e., gait speed) are lower in older aged animals; (2) explored the relationship between performance in a novel task of executive function (Wake Forest Maze Task-WFMT) and a well-established assessment of working memory (delayed response task-DR task); and (3) examined the association between baseline gait speed with executive function and working memory at 1-year follow-up. We found (1) physical and cognitive declines with age; (2) strong agreement between performance in the novel WFMT and DR task; and (3) that slow gait is associated with poor cognitive performance in both domains. Our results suggest that older aged vervets exhibit a coordinated suite of traits consistent with human aging and that slow gait may be a biomarker of cognitive decline. This integrative approach provides evidence that gait speed and cognitive function differ across the lifespan in female vervet monkeys, which advances them as a model that could be used to dissect relationships between trajectories of dual decline over time.


Assuntos
Função Executiva , Marcha , Envelhecimento , Animais , Chlorocebus aethiops , Cognição , Feminino , Velocidade de Caminhada
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